July 7, 2022 | Few diagnostic exams delineate between cancer patients who will benefit from chemotherapy and those who can safely pursue alternative treatments. In fact, before an Australian-American research team published a study in the New England Journal of Medicine (DOI: 10.1056/NEJMoa2200075) earlier this month, no documented blood tests were considered substantial enough to inform colon cancer diagnostic and treatment decision-making.
An international team of researchers from the Walter and Eliza Hall Institute (WEHI) of Medical Research in Melbourne, Australia and Johns Hopkins Sydney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, co-led a study to predict which stage II colon cancer patients would likely need chemotherapy after the surgical removal of cancerous tissue.
Out of an abundance of caution and in an attempt to lower the 20% recurrence rate, physicians offer adjuvant chemotherapy to all stage II colon cancer patients. This cancer stage extends beyond the colon wall but not to lymph nodes or other organs. With nearly 4,000 Australians diagnosed each year, many patients receive chemotherapy unnecessarily.
Novel Diagnostic Blood Testing
Together, the international team designed a circulating tumor DNA (ct-DNA) blood test with the ability to predict disease course and suggest the safe use of alternative treatment options.
“While chemotherapy can be essential and lifesaving, many patients are receiving the treatment and its associated toxicities without any benefit,” said Jeanne Tie, Co-Lead Author, WEHI Associate Professor, and Peter McCallum Cancer Centre Medical Oncologist, in a press release. “This ctDNA blood test could be used to spare around 600 Australians and over 100,000 people worldwide from unnecessary chemo treatments each year.”
Circulating tumor DNA releases into the bloodstream after a tumor cell dies, expels its contents, and leaves new tumor cells to take its place. Therefore, ctDNA in the blood at approximately four to seven weeks post-surgery strongly indicates cancer growth and micrometastases–the process of cancer cells traveling in the blood and establishing residence in other organs.
The newly emerging cancer cells are undetectable to radiologic imaging, making it virtually impossible to determine if a patient is cancer-free under existing diagnostic measures. “Our trial has conclusively shown how the ctDNA blood test can be used to direct post-surgical therapy in stage II colon cancer and substantially reduce the number of patients treated with chemotherapy, without impacting the risk of cancer relapse,” said Tie. “We found that when a patient’s blood test does not reveal ctDNA after colon surgery, the likelihood of micrometastases is very low, and chemotherapy can be avoided as there are no tumor fragments left to kill.”
With more than 450 patients across 23 Australian hospitals, the team completed the world’s first randomized trial using ctDNA blood tests with enough significant results to suggest its use as an oncologic clinical care staple.
“The collaborative efforts from these hospitals were critical for us to complete this trial, the first randomized trial in any solid tumor type worldwide that used a blood test to determine which patients can safely forgo chemotherapy after surgery,” said Co-Lead Author and WEHI Associate Professor Peter Gibbs. “Randomized studies like this are needed to deliver meaningful patient outcomes, but they are not possible without the support of our collaborators and philanthropic efforts.”
The team has its eyes set on more than colon cancer. Similar trials exist for other diseases, such as pancreatic and ovarian cancer. “Our ctDNA test can be used to reduce the physical and financial toxicity brought on by unnecessary chemo treatments and believe our findings bring us closer to significantly improving treatment options for many patients across a broad range of cancer types,” hopes Gibbs.